The factors which control local bone cell function during growth, aging and disease are poorly understood. This is due in part to the complex structural organization of bone tissue. Isolated cell populations enriched in specific types of bone cells (osteoblasts, osteoclasts or osteocytes) provide excellent model systems for simplifying this tissue and examining the effects of hormones and pharmacologic agents on cell function. The experiments described in this proposal are designed to investigate the influence of hormonal agents and in vitro aging on specific biochemical properties of an osteoblast-enriched population of cells isolated from adult rabbits. The biochemical properties to be studied include: macromolecular synthesis (total protein synthesis, RNA synthesis, DNA synthesis), collagen synthesis, phosphatase enzyme activity, citrate decarboxylation and cyclic nucleotide metabolism. The problem of age-related loss skeletal mass is reflected in the fact that as many as 190,000 hip fractures, 180,000 vertebral fractures and 90,000 broken forearms are caused each year by osteoporosis. The underlying factors involved in skeletal aging are unknown. With this in mind the primary objective of this proposal is to establish an in vitro model to examine osteoblasts isolated from adult rabbits. The specific aims are to answer the following questions: (1) How do hormones known to influence bone physiology influence certain biochemical properties of isolated osteoblasts? (2) What is the effect of in vitro aging on the biochemical properties? (3) How does in vitro aging effect the response of osteoblasts to hormonal stimulation? The model employed in these experiments and the results of these studies will provide the basis for future studies on osteoblasts isolated from both aged and experimentally manipulated animals.